GA Grphi Approh o piemiology he GA frme Grphi Apprisl ool for piemiology Grphi Arhiteturl ool for piemiology the shpe of every epiemiologil stuy GA stuy esign () GA stuy nlyses (G & G) G G GA stuy pprisl (RAMMo) Reruitment Allotion Mintenne Mesurement: lin or ojetive GA stuy pplition rtiipnts Allotion xposure Group Mintenne ime Mesure Reruitment omprison Group utomes 1
GA stuy esign () rtiipnts rtiipnts Stuy Setting xposure Group omprison Group ligile rtiipnts ime utomes rtiipnts xposure & omprison Groups utomes () xposure or Intervention Group (G) G G omprison or ontrol Group (G) Dis-ese yes no utomes () ime () GA stuy esign () rtiipnts xposure Group omprison Group ime utomes 2
GA stuy nlyses All epiemiologil stuies involve mesuring the URRN of isese urrene = Numertor Denomintor D N Denomintor (rtiipnts) = N D Numertor (utomes) GA stuy nlyses urrene = N D verll Denomintor Denomintor 1: xposure Group G G G Denomintor 2: omprison Group G Denomintor 1: xposure Group G G G Denomintor 2: omprison Group G Numertor 1: Numertor 2: Numertor 1: Numertor 2: xposure Group urrene: G = G omprison Group urrene: G = G stimting effets & ssoitions involves ompring ourrenes Reltive ffet or Risk = G G e.g. reltive risk (RR), risk rtio, prevlene rtio, iniene rtio Asolute ffet or Risk Differene = G - G Anlyses it s ll out G & G e.g. risk ifferene (RD), solute risk Numer Neee o ret (NN) = 1 RD 3
urrene = N D per unit of time GA stuy pprisl (RAMMo) Reruitment Denomintor 1: xposure Group G x Numertor 1= xposure Group urrene: G = (G x ) G G person-time exposure Denomintor 2: omprison Group G x Numertor 2 = omprison Group urrene: G = (G x ) Allotion Mintenne Mesurement: lin or ojetive Stuy pprisl How well (or firly ) ws the stuy one? Ws it fir ( ) or poor ( )? RAMMo fir Reruitment? prtiipnts representtive of trget popultion fir hs two menings: lne ok ( firly well one ) no stuy is perfet Stuy setting & eligiility riteri well esrie? Reruit rnom smple R Reruit onseutive eligiles RAMMo RAMMo G G fir Allotion? were G & G omprle Allotion proess well esrie? If llote y investigtors: Allote rnomly AND onele llotion R If llote y mesurement: Ajuste for ifferenes etween G & G (e.g. sttistil or mthing) G G fir Mintenne? i prtiipnts remin in llote groups (G & G) rtiipnts &/or investigtors lin to exposure (n omprison exposure)? ompline resonle & similr ontmintion low & similr o-interventions low & similr ompleteness of follow-up high & similr 4
RAMMo RAMMo G G fir Mesurement? of utomes Mesurement proess well esrie G G fir Mesurement? of G & G if llote y mesurement (not rnomly) Mesurement proess well esrie Mesurement proess similr for ll prtiipnts Mesurement proess similr for ll prtiipnts If mesurement not ojetive (eg. utomte or efinitive) were ssessors lin to exposure (n omprison exposure) If mesurement not ojetive (eg. utomte or efinitive) were ssessors lin to the stuy outome when mesuring exposure sttus GA stuy pplition X-ftor: mking eviene-se eisions rtiipnts Allotion Reruitment piemiologi eviene xposure Group omprison Group oliy issues tient preferenes ime Mintenne Mesure utomes linil onsiertions professionl expertise: putting it ll together - the rt of prtie he GA pproh: every epiemiologil stuy hngs on the GA frme there is only one si stuy esign: ohort (& se-ontrol) stuies - etiology / prognosis / intervention R ( rnomise ohort stuy)- interventions ross-setionl stuies - ignosis ohort (follow-up) stuy: rhetypl epiemiologil pproh rtiipnts xposure Group ime Allote y mesurement (not y rnomistion) omprison Group utomes etiology (risk), non rnomise interventions, prognosis 5
Rnomise ontrolle tril - ohort stuy where exposure llote y rnomistion proess rtiipnts Allote y rnomistion se series is ohort stuy with no omprison group rtiipnts Allote y mesurement xposure Group omprison Group xposure Group ime utomes ime utomes Before-fter stuy ross-over tril rtiipnts rtiipnts Allote y mesurement Allote y rnomistion omprison Group xposure Group 1 1 2 omprison Group 2 xposure Group xposure Group 2 2 1 omprison Group 1 ime utomes ime utomes rel-life time ross-setionl stuy rtiipnts Dignosti test ury stuy Allote y mesurement Disese +ve G G Disese -ve xposure Group omprison Group utomes ime revlene n ignosti test ury stuies est + Likelihoo +ve test if D+ve: G = G - +ve LR = G G Likelihoo +ve test if D -ve: G = G 6
Dignosti test ury stuy Dignosti test for isese preition Disese +ve G G Disese -ve est +ve G G est -ve est + Likelihoo -ve test if D+ve: G = G - -ve LR = G G Likelihoo -ve test if D -ve: G = G + Disese - Likelihoo of D if test +ve: G = G ositive preitive vlue Likelihoo of no D if test -ve G = G Negtive preitive vlue se ontrol stuy (neste in rel or virtul ohort stuy) rtiipnts GA: multiple tegories rtiipnts Allote y mesurement xposure Group ime omprison Group ontrols ses utomes Multiple xposure tegories Multiple utome tegories 1 2 3 omprison etiology (risk), non rnomise interventions GA: ontinuous mesurements rtiipnts ontinuous mesure of xposure: e.g. oy mss inex high..me..low orreltion oeffiient Life is non-rnomise tril ontinuous mesure of utomes e.g. lipis low meium high 7
A forms: (in xel) Intervention Dignosis rognosis/risk Systemti Reviews ownlo from: www. epiq.o.nz Rpi pprisl: GA-lite ritil pprisl of rnomise ontrolle tril All epi stuies n e hung on the GA frme Hulley et l. HRS stuy JAMA 1998;280:605-13 Moel nswer on www.epiq.o.nz is for rtiipnts ligile opultion: ost-menopusl, estlishe HD, < 80 yrs, no MI in lst 6 mths, no HR lst 3 months Setting: 68,561 women sreene from 20 outptients/ommunity sreening entres & re for xposure & omprison HR (n=1380) Ientil leo (n=1383) rtiipnts: ll eligiles invite who onsente (2763) xposure () [intervention] omprison () [ontrol] 8
is for utome is for utome 2º outome: HD eth men HDL holesterol (mmol/l) HR leo yes no 71 58 utomes () 1.4 1.27 utomes () tegoril t (yes/no exmple) ontinuous t (mens exmple) is for ime is for ime ime () yes no HD outomes mesure over 4.1 yers (longituinl) 71 58 2º outome: HD eth utomes () HDL holesterol mesure t 1 yer (ross-setionl) HR leo 1.4 1.27 men HDL holesterol utomes () GA & for HRS GA: ourrene = numertor enomintor rtiipnts = women with HD 2763 = xposure = HR 1380 1383 omprison = pleo xp. Group urrene G = (G x ) G = G = omp. Group urrene G = (G x ) ime = 4.1 yrs 71 58 utome = HD eth = = = = = 9
HRS: when ourrene = HD eth* = 2763 xp. Group urrene G = Gx = 71 (1380 x 4.1) = 12.6 /1000/yr = 4.1 yrs G= 1380 = 71 G= 1383 = 58 utomes (HD eth) omp. Group urrene G = Gx = 58 (1383 x 4.1) = 10.2/1000/yr stimting effets & ssoitions: HR & HD eth Reltive ffet or Risk = G G 12.6 / 1000/yr 10.2 / 1000/yr = 1.23 Asolute ffet or Risk Differene = G - G 12.6 / 1000/yr - 10.2 / 1000/yr = 2.4 / 1000/yr Numer Neee o ret (NN) = 1 RD = 1 2.4/1000/y = 1 eth per 432 on HR for yer reision of ffets: (95% onfiene intervls & p-vlues) Reltive ffet/risk (RR) = 1.24 (95% I: 0.87, 1.75), p = 0.23 Asolute ffet/risk Differene (RD) = 2.4 / 1000/yr (-1.69, 6.34) Numer Neee to ret (NN) to use 1 eth = 432 per yr (-592 to to 158) rtiipnts xposure omprison utome ime Apprise the eviene using RAMMo n the GA frme Reruitment Allotion Mintenne Mesurement lin or ojetive Ws there fir Reruitment proess? ligile opultion: ost-menopusl, estlishe HD, < 80 yrs, no MI in lst 6 mths, no HR lst 3 months (? Numers eligile) Setting: 68,561 women sreene from 20 outptients/ommunity sreening entres rtiipnts: ll eligiles invite (2763) 10
Ws the Allotion to & fir? R - rnomly llote, llotion onele HR (n=1380) xposure () [intervention] rnom llotion omprison () [ontrol] onele llotion (tmper-proof) Ientil leo (n=1383) HRS: seline hrteristis (tle 1) HR (n=1380) Age (yrs) Smoking (%) SB (mmhg) A inhiitors (%) G 67 13 135 17 G 67 13 135 18 leo (n=1383) pge 608 Alloting prtiipnts rnomly to G & G usully proues similr rnge of hrteristis in eh group Nurses Helth (ohort) Stuy: seline hrteristis (tle 1) urrent HR G G No HR Ws there fir Mintenne - i prtiipnts remin in llote groups throughout stuy? HR (n=1380) leo (n=1383) High B (%) Smoking (%) High BMI (%) st use (%) 23 11 10 34 22 14.5 Alloting prtiipnts y mesurement to G & G often results in ifferent rnge of hrteristis in eh group 15 24 ompline: % who keep tking or? -high ompleteness of follow-up: wht % of G & G f/up? -high Di it iffer etween Groups? -no Bline: prtiipnt? -yes rtitioners? -yes ontmintion: % of who get (& vie vers)? -low o-intervention: i G or G reeive other interventions? If so, i it iffer etween Groups? -sttin use iffere Ws there fir Mesurements of outomes: lin or ojetive? yes no G G 172 176 lin: were ssessors of outomes wre of whih Group (G or G) prtiipnts were in? - no 1º outome: non ftl MI or HD eth utomes () ojetive: were outomes ssesse using ojetive mesures (e.g. tissue smple, sn, vlite Questionnire? - yes Apprisl of vliity, effet size & preision R-multiple reruitment strtegies, well esrie inlusion riteri, proly representtive of US women with HD, lthough numers not given. A-rnomly llote, onele llotion (ientil tlets), plus juste in nlyses for minor ifferenes etween G & G M-100% mortlity & 99% 1 outome f/u, goo, minly trete eqully euse tretment line Mo-1 outome se on stnrise, resonly ojetive lgorithm & ssesse lin to exposure *Hulley et l. HRS JAMA. 1998;280:605-613 11